Project Summary Visual neurons are strongly influenced by sensory history or adaptation. Our long-term goal is to understand how such experience influences cortical processing and contributes to vision. Adaptation effects have been described throughout the visual system, from the retina to higher visual cortex. Almost without exception, these effects have been measured in individual neurons. This is problematic, as it is widely believed that sensory information is encoded and processed by neuronal populations distributed across multiple cortical areas. Population coding is not adequately described by the mean tuning functions of individual neurons; it can be strongly influence by the coordination of activity among cells. How adaptation affects population coding is poorly understood, hampering our understanding of how experience driven changes in cortical circuits contribute to visual experience. In this proposal, we make use of recent theoretical work in understanding population coding, to test how adaptation influences the encoding of stimulus orientation by populations of neurons distributed across multiple stages of the macaque visual system. In specific aim 1, we will determine how brief periods of adaptation affect neuronal tuning, response variability and response correlations, in the primary visual cortex (V1) and area V4 of awake monkeys performing a fixation task. In specific aim 2, we will relate changes in population responses in V1 and V4 to the animal's performance on a fine orientation discrimination task. We will test algorithms for estimating stimulus orientation from the measured population responses and we will compare these with algorithms that best predict the animals' perceptual decisions, in both control and adapted states. This will reveal how animals weight the sensory responses to make perceptual decisions, how this weighting corresponds to the theoretically-optimal for estimating orientation, and how that weighting is altered by experience-driven plasticity. In specific aim 3, we will conduct complementary experiments, with a more mechanistic focus. We will use a novel recording arrangement to measure simultaneously the activity of an output population in V1 and its downstream targets in V2 in anesthetized animals. We will determine how adaptation alters the functional coupling between these networks, and how coupling depends on the experience-driven changes in single neuronal properties and ensemble responses. Our project will provide the first comprehensive view of how population responses in visual cortex are affected by recent history, and how population responses are interpreted by downstream networks, to give rise to perceptual experience. The combination of recently-developed tools will allow us to bring unprecedented power to addressing these central and basic issues. We expect this project will contribute broadly to our understanding of population coding, corticocortical communication, and plasticity. The knowledge gained should be invaluable for developing more effective devices for interpreting brain activity for prosthetic devices, and for understanding the coordination of activity within and between cortical areas, in health and disease.